Recommendations for research

The guideline committee has made the following recommendations for research. The committee's full set of research recommendations is detailed in the full guideline.

As part of the 2017 update, the standing committee made an additional research recommendation on BRCA1 mutations in unselected basal phenotype and triple negative breast cancer. The committee also extended the research recommendation on chemoprevention to include the aromatase inhibitors exemestane and letrozole. Details can be found in the 2017 addendum.

1 Carrier probability calculation models

Further research is recommended into developing and validating models for calculating carrier probability, which incorporate additional data, such as the molecular pathology of tumours and the prevalence of mutations in different ethnic groups. [2013]

Why this is important

This guideline recommends offering genetic testing to people with a 10% likelihood of carrying a BRCA1/2 mutation. Models to assess the likelihood of a BRCA1/2 mutation need to be improved because their estimates still have wide confidence margins. Models are sensitive to population prevalence of mutations and need adjustment for pathological subtypes of breast and ovarian cancer, which are particularly associated with BRCA1 mutations. Improving the predictive powers of these models will provide more cost-effective testing.

2 Rapid genetic testing

Research is recommended to determine the benefits and harms of creating rapid access to genetic testing for people with newly diagnosed breast cancer. This research should address the optimum model for service delivery and organisation, the clinical and cost effectiveness of such a change, uptake outcomes and patients' experience. [2013]

Why this is important

There is no clear evidence base for rapid genetic testing at the time of diagnosis of primary breast cancer. Knowledge of genetic status may increase uptake of risk-reducing mastectomy and in future guide first-line chemotherapy. To be useful for such decision-making, results of genetic tests are needed within 4 weeks of diagnosis. This creates logistic problems in providing enough information for considered decision-making and delivering results of genetic tests in a supportive environment. Some guideline committee members were of the opinion that people had enough to cope with shortly after diagnosis without additional worries about genetic testing. However, others thought that early knowledge of genetic status would help decisions about surgery thus avoiding the need to consider this at a future date. For example, initial treatment by wide local excision often necessitates radiotherapy, which makes an acceptable cosmetic operation more challenging. Genetic counselling to facilitate such decisions soon after diagnosis would require reorganisation of current services.

3 Benefits of MRI surveillance in women over 50 years

Research is recommended to establish the risk and benefits of MRI surveillance compared with mammography in women over 50 years with a personal history of breast cancer. Studies should include sub-analysis for breast density. [2013]

Why this is important

There have been at least 6 large trials of MRI surveillance in women at high risk of breast cancer. However, none of these contained enough women to assess the potential benefit of MRI over mammography alone in women over 50 years. After 50 years of age, mammography becomes more sensitive and the trade-off between sensitivity and specificity may make MRI less cost effective. Although breast density decreases with age, and particularly after the menopause, there is no sudden change at any particular age. For this reason breast density should be included as a confounding variable.

4 Chemoprevention to reduce incidence of breast cancer

What is the clinical and cost effectiveness of aromatase inhibitors (particularly exemestane and letrozole) compared with tamoxifen and raloxifene for reducing the incidence of breast cancer in women with a family history of breast or ovarian cancer? [2017]

Why this is important

One randomised controlled trial (RCT) showed anastrozole to be effective for the primary prevention of breast cancer. However, there has been no RCT of other third-generation aromatase inhibitors, such as exemestane and letrozole. Exemestane is not strictly from the same class as anastrozole (and may therefore have different modes of action). More information on the efficacy of these other aromatase inhibitors may offer more options for chemoprevention for women at risk of breast cancer.

5 Impact of risk-reducing surgery

Further research is recommended to compare psychosocial and clinical outcomes in women who choose and women who do not choose to have risk-reducing surgery. [2013]

Why this is important

Many women are happy with their decision to undergo risk-reducing surgery. However, some women do subsequently regret this choice. A greater understanding of the factors that predict satisfaction or regret will help to guide women's choices in the future. Studies show that risk-reducing surgery significantly reduces risk of breast cancer, but there is insufficient evidence to decide between, for example, skin-sparing mastectomy and total mastectomy. The pros and cons of risk-reducing surgery in women with a diagnosis of cancer also need further study.

Why this is important

The association of breast cancer with BRCA1 mutations was originally with the basal phenotype. Although triple negative breast cancer has been used as a proxy for the basal phenotype, they do not fully overlap. Badve et al. (2010) found that 71% of triple negative breast cancers were basal like and 77% of basal-like cancers were triple negative. Triple negative breast cancer has been adopted as a proxy for the basal phenotype because most pathology laboratories test for triple negative cancer as a standard. Rakha et al. (2009) found that the basal phenotype has a high positive predictive for the BRCA1 mutation. A study of the prevalence of BRCA1 mutations would be useful because we may be missing these in basal phenotype breast cancers that are not are not tested as standard. This information would indicate whether BRCA1 testing is helpful for basal phenotype cancers.